1380P Phase (Ph) II study of zanidatamab + chemotherapy (chemo) in first-line (1L) HER2 expressing gastroesophageal adenocarcinoma (GEA)

216 Background: Despite a large number of randomized trials, there is no consensus as to the best regimen for advanced gastroesophageal cancer. Combination therapy with docetaxel, cisplatin, and 5-FU has shown increased response rates, progression-free survival (PFS) and overall survival (OS), but at the cost of significant toxicity. Based on a small phase II study, FLOT has been adopted by some groups given its better toxicity profile. We aim at reporting our experience with this regimen Methods: Patients with unresectable advanced gastroesophageal adenocarcinoma who received FLOT (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, and fluorouracil 2600 mg/m2 as a 24h infusion in combination with docetaxel 50 mg/m2 on day 1 every 2 weeks) as first-line therapy at our institution were retrospectively evaluated. PFS and OS were estimated by the Kaplan-Meier method. Results: A total of 23 patients were reviewed, most of them with metastatic disease (60%). Median age was 56 years (range 26–76) and 74% were male. Median PFS and OS were 5,2 (95% CI 4,0-6,3) and 8,5 months (95% CI 4,4-12,6), respectively. Only 13%of the patients experienced prolonged PFS (>12 months). There were no deaths due to the treatment. Conclusions: Before FLOT could be adopted as a first-line regimen for metastatic gastroesophageal cancer, phase III trials are urgently needed comparing FLOT with more traditional regimens.

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Ramucirumab and irinotecan in patients with previously treated gastroesophageal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.tps4150 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. TPS4150-TPS4150

Author(s):

Haeseong Park ◽

Nikolaos Trikalinos ◽

Aravind Sanjeevaiah ◽

Katrina Pedersen ◽

Nusayba Ali Bagegni ◽

...

Keyword(s):

Clinical Trial ◽

Survival Time ◽

Disease Progression ◽

Progression Free Survival ◽

Combination Regimen ◽

Gastroesophageal Cancer ◽

First Line ◽

Free Survival ◽

Gastroesophageal Adenocarcinoma ◽

Line Chemotherapy

TPS4150 Background: Ramucirumab is used for treatment of metastatic gastroesophageal adenocarcinoma after disease progression on first-line chemotherapy. Superior survival outcome is expected when combined with paclitaxel. However, many patients suffer from neuropathy after oxaliplatin-containing first-line chemotherapy and are unable to tolerate paclitaxel. Irinotecan has shown survival benefit as a single agent or in combination with other agents, but has not been used in combination with ramucirumab for treatment with gastroesophageal cancer. We hypothesize that this combination regimen of irinotecan plus ramucirumab administered as second-line treatment will be well-tolerated with improved outcomes similar to paclitaxel plus ramucirumab in patients with advanced gastroesophageal cancer. Circulating levels of angiogenic factors are correlatives of particular interest in this study. Methods: This is a multi-institutional, single-arm phase II clinical trial of ramucirumab and irinotecan. Primary objective of the study is to determine the progression-free survival in patients treated with this combination after disease progression on first-line chemotherapy. Secondary objectives are to determine other indices of efficacy including overall survival, time to progression, objective response rate, and clinical benefit rate; and to evaluate toxicity and tolerability. Patients with confirmed diagnosis of gastroesophageal adenocarcinoma with measurable disease are included. Patients are required of have disease progression during or within 4 months of first line chemotherapy. Key exclusion criteria include squamous histology; prior irinotecan or ramucirumab use; active brain metastases; or other contraindications to ramucirumab including recent history of gastrointestinal bleeding or perforation, thromboembolic event, and uncontrolled hypertension. Patients receive ramucirumab 8mg/kg with irinotecan 180mg/m2 IV every 14 days. We plan to enroll 40 patients which will provide 85% power at a 0.05 significance level to detect a median progression free survival time of 4 months compared to historic control of 2.5 months. 25% of patient accrual is complete as of February 2019. Clinical trial information: NCT03141034.

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Real-world outcomes of first-line U.S. patients with unresectable advanced or metastatic gastroesophageal adenocarcinoma by primary tumor location.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.304 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 304-304

Author(s):

Veena Shankaran ◽

Hong Xiao ◽

David Bertwistle ◽

Ying Zhang ◽

Pranav Abraham ◽

...

Keyword(s):

Gastric Cancer ◽

Real World ◽

Gastroesophageal Junction ◽

Tumor Location ◽

Rank Test ◽

First Line ◽

Eligibility Criteria ◽

Cox Models ◽

Significant Difference ◽

Gastroesophageal Adenocarcinoma

304 Background: Gastric cancer clinical trials are inconsistent in their inclusion of esophageal adenocarcinoma (EAC). Thus it is uncertain if outcomes are similar among subgroups of gastroesophageal adenocarcinoma. The aim of this study was to compare baseline characteristics and clinical outcomes of US patients with EAC versus Gastroesophageal Junction Cancer (GEJC) and Gastric Cancer (GC) treated in real world clinical settings. Methods: Adult patients with unresectable, advanced or metastatic GC, GEJC, or EAC diagnosed between January 2011 and November 2018 were identified from the Flatiron Health database. Patients with a positive HER2 test, or who received trastuzumab, were excluded. Overall survival (OS) was defined as time from first-line (1L) treatment initiation to death or loss of follow-up. Survival analyses were conducted using Kaplan-Meier methods with log-rank test and Cox models. Results: A total of 3052 patients (969 EAC and 2083 GEJC/GC) met eligibility criteria. Out of all EAC patients, 90% were males and 76% were white. Within the GEJC/GC patients, 67% were males and 57% were white. Median age was 66 years for both cohorts while proportion with ECOG PS of 0 or 1 was 78% for EAC and 84% for GEJC/GC among patients with ECOG scores. The proportion of patients receiving 1L treatment was comparable (78% for EAC, 76% for GEJC/GC) across groups with FOLFOX being the most frequent treatment (25% for EAC and 29% for GEJC/GC). There was no significant difference in OS between the two groups, with median OS of 9.1 and 9.6 months for EAC and GEJC/GC, respectively (HR 0.957, 95% CI: 0.863 - 1.062, p = 0.41). Conclusions: In this US real-world analysis, OS did not differ significantly between patients with EAC and patients with GEJC/GC who received 1L treatment, suggesting that these two populations may have comparable survival benefit from systemic therapy.

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Timed‑flat infusion of 5‑fluorouracil with docetaxel and oxaliplatin as first‑line treatment of gastroesophageal adenocarcinoma: A single institution experience with the FD/FOx regimen

Oncology Reports ◽

10.3892/or.2018.6475 ◽

2018 ◽

Cited By ~ 2

Author(s):

Alessio Cortellini ◽

Katia Cannita ◽

Alessandro Parisi ◽

Olga Venditti ◽

Paola Lanfiuti Baldi ◽

...

Keyword(s):

Line Treatment ◽

Single Institution ◽

First Line ◽

Gastroesophageal Adenocarcinoma ◽

First Line Treatment

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Multicenter phase III comparison of cisplatin/S-1 (CS) with cisplatin/5-FU (CF) as first-line therapy in patients with advanced gastric cancer (FLAGS): Secondary and subset analyses

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4511 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4511-4511 ◽

Cited By ~ 4

Author(s):

J. A. Ajani ◽

W. Rodriquez ◽

G. Bodoky ◽

V. Moiseyenko ◽

M. Lichinitser ◽

...

Keyword(s):

Median Survival ◽

Phase Iii ◽

Diffuse Type ◽

Control Effect ◽

First Line ◽

Primary Analysis ◽

First Line Therapy ◽

Multicenter Phase ◽

Line Therapy ◽

Gastroesophageal Adenocarcinoma

4511 Background: The primary analysis of FLAGS (ASCO-GI-2009) showed that CS and CF had similar overall survival (OS) but CS had a significantly superior safety profile. Methods: 1,053 (1,029 treated; CS=521/CF=508) patients with untreated, advanced gastric/gastroesophageal adenocarcinoma were randomized to either S-1 (25 mg/m2 bid, d 1–21)/cisplatin (75 mg/m2 d 1) q 28 d or 5-FU (1,000 mg/m2/d 5-d infusion)/cisplatin (100 mg/m2 d 1) q 28 d. OS analyses for non-inferiority (NI), by pre-specified stratifications, and by the largest histologic subset (diffuse type histology) were performed. Results: OS for NI: OS from CS compared to CF had a HR=0.92 (two-sided 95% CI, 0.80–1.05). HR=1.05 being much lower than HR=1.22 derived from the literature. Using a stringent HR non-inferiority margin of 1.10, CS remains statistically significantly non-inferior (p=0.0068) to CF. The 74% preserved control effect by CS is well above the suggested 50% by Rothmann et al. (Statist-Med2003;22:239–264). OS by stratifications: Of 12 stratification sub-categories, CS produced OS HR=<1.0 in 9 and HR=>1.0 in 3. Subset analysis: OS analysis for diffuse type histology (n=590) showed that CS (median survival=9.0 months) resulted in a superior OS (Log rank p=0.0413; HR, 0.83 [95% CI, 0.70 to 0.99]) than CF (median survival=7.1 months). Conclusions: CS is statistically non-inferior to CF while proving much safer for the patients. CS resulted in a HR=<1.0 in the majority of pre-specified stratifications and CS produced statistically superior OS for patients with diffuse type histology (needs prospective studies). CS is an optimum substitute for CF. Supported by Taiho Pharma, USA. No significant financial relationships to disclose.

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External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Therapeutic Advances in Medical Oncology ◽

10.1177/17588359211019672 ◽

2021 ◽

Vol 13 ◽

pp. 175883592110196

Author(s):

Paula Jimenez-Fonseca ◽

Alberto Carmona-Bayonas ◽

Alba Martinez-Torron ◽

Maria Alsina ◽

Ana Custodio ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

External Validity ◽

Meta Analysis ◽

Phase Iii ◽

Line Treatment ◽

First Line ◽

Her2 Positive ◽

Gastroesophageal Adenocarcinoma ◽

First Line Treatment

Background: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1–21.0) versus ToGA regimens (7.5, 6.4–8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25–3.09). The results achieved with CAPOX–trastuzumab were comparable to those attained with ToGA regimens. FOLFOX–trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24–0.92) compared with IHC 3+ (HR 0.69, 0.49–0.96), and in diffuse (HR 0.37, 0.20–0.69) versus intestinal-type tumors (HR 0.76, 0.54–1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX–trastuzumab in clinical practice and point toward a possible benefit of FOLFOX–trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.

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Patient-reported outcomes from the phase II FAST trial of zolbetuximab plus EOX compared to EOX alone as first-line treatment of patients with metastatic CLDN18.2+ gastroesophageal adenocarcinoma

Gastric Cancer ◽

10.1007/s10120-020-01153-6 ◽

2021 ◽

Vol 24 (3) ◽

pp. 721-730

Author(s):

Florian Lordick ◽

Salah-Eddin Al-Batran ◽

Arijit Ganguli ◽

Robert Morlock ◽

Ugur Sahin ◽

...

Keyword(s):

Disease Progression ◽

Repeated Measures ◽

Patient Reported Outcomes ◽

Statistical Significance ◽

Symptom Burden ◽

Progression Free Survival ◽

First Line ◽

Patient Reported ◽

Gastroesophageal Adenocarcinoma ◽

Eortc Qlq

Abstract Background Zolbetuximab plus first-line EOX (epirubicin, oxaliplatin, capecitabine; ZOL/EOX) significantly prolonged progression-free survival and overall survival in the FAST trial vs EOX alone. We report the patient-reported outcomes (PROs) of FAST in patients with advanced gastroesophageal adenocarcinoma. Methods Patients were randomized to ZOL/EOX or EOX alone. Patients could receive ≤ 8 EOX cycles and remained on zolbetuximab until disease progression. PROs were collected using the EORTC QLQ-C30 and QLQ-STO22 before drug administration at day 1/cycle 1, day 1/cycle 5, end of EOX treatment, and q12w thereafter until disease progression. Time to deterioration (TTD), defined as the first meaningful worsening from baseline, in the individual QLQ-C30/QLQ-STO22 scores was analyzed. Longitudinal changes in scores from baseline were analyzed using a mixed-effects model for repeated measures (MMRM). Results The per protocol population included 143 (ZOL/EOX: 69; EOX: 74) patients. Baseline QLQ-C30 and STO22 scores were comparable between arms and denoted intermediate-to-high quality of life (QoL), intermediate-to-low global health status (GHS) and low symptom burden. Descriptive analyses showed no differences between arms until end of EOX but maintenance therapy with zolbetuximab was associated with better QoL and less symptom burden thereafter. TTD for most scores favored ZOL/EOX over EOX and reached statistical significance for GHS (p = 0.008). MMRM results support TTD findings; no statistically significant differences were observed between arms in any score except for nausea and vomiting (p = 0.0181 favoring EOX). Conclusions ZOL/EOX allowed patients to maintain good QoL and low symptom burden for longer than EOX alone.

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